U.S. Pat. No. 5,516,790 (issued May 14, 1996) suggests a method of inhibiting estrogen activity by administering a biologically active amount of a substituted dibenzofuran or substituted dibenzodioxin.
U.S. Pat. No. 5,948,808 (issued Sep. 7, 1999) offers compounds and compositions of substituted indole-3-carbinols and diindolylmethane suitable for treating estrogen-dependent tumors along with methods of treating such cancerous-conditions.
U.S. Pat. No. 6,136,845 (issued Oct. 24, 2000) suggests methods and pharmaceutical combinations for inhibiting estrogen-dependent tumors via the co-administration of antiestrogen triphenylethylenes, including tamoxifen and alkyl PCDFs.
Brockman, et al. (“Activation of PPARγ leads to inhibition of anchorage independent growth of human colorectal cancer cells” Gastroenterology 115:1049–1055, 1998) suggests that PPAR agonists will be effective antitumorigenic agents for treatment of colorectal cancer.
Chen, et al. (“Aryl Hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane,” Carcinogenesis, 19:1631–1639, 1998) states that DIM represents a new class of relatively non-toxic AhR-based antiestrogens that inhibit E2-dependent tumor growth in rodents.
Chen, et al. (“Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells” Biochem. Pharmacol. 51:1069–1076, 1996) suggests that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced CYP1A1-dependent ethoxyresorufin O-deethylase (EROD) activity in human breast cells, and co-treatment with TCDD plus different concentrations of I3C or DIM resulted in a significant decrease in the induced response at the highest concentration of I3C or DIM.
Duan, et al. (“Estrogen receptor-mediated activation of the serum response element in MCF-7 cells through MAPK-dependent phosphorylation of Elk-1” J. Biol. Chem. 276:11590–11598, 2001) suggests that transcriptional activation of the serum response element by E2 was due to ERalpha activation of the MAPK pathway and increased binding of the serum response factor and Elk-1 to the serum response element.
Elstner, et al. (“Ligands for peroxisome proliferator-activated receptor gamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice” Proc. Natl. Acad Sci. USA 95:8806–8811, 1998) suggests that combined administration of troglitazone and all-trans-retinoic acid causes prominent apoptosis and fibrosis of MCF7 tumors in triple immunodeficient mice without toxic effects on the mice.
Garcia, et al. (“Constitutive activation of Stat3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells” Oncogene 20:2499–2513, 2001) suggests that tyrosine kinases transduce signals through Stat3 protein that contribute to the growth and survival of human breast cancer cells in culture and potentially in vivo.
Jeng, et al. (“Role of MAP kinase in the enhanced cell proliferation of long term estrogen deprived human breast cancer cells” Breast Cancer Res. Treat. 62:167–175, 2000) suggests that the MAP kinase pathway is, in part, involved in the adaptive process which results in enhanced DNA synthesis and cell proliferation in the absence of exogenous estrogen in estradiol long term cells.
McDougal and Safe (“Methyl-substituted diindolylmethanes as AhR-based antitumorigenic/antiestrogenic compounds” Organohalogen Compounds, 37:253–256, 1998) suggests that methyl substituted DIMs inhibit estrogen induced breast cancer growth.
McDougal, et al. (“Inhibition of carcinogen-induced rat mammary tumor growth and other estrogen-dependent responses by symmetrical dihalo-substituted analogs of diindolylmethane” Cancer Letts., 151:169–179, 2000) suggests that dihalo-substituted analogs of diindolylmethane significantly inhibited mammary tumor growth while no significant changes in organ weights or liver and kidney histopathology were observed.
Michaud, et al. (“Fruit and vegetable intake and incidence of bladder cancer in a male prospective cohort” J. Natl. Cancer Inst., 91:605–613, 1999) suggests that high cruciferous vegetable consumption may reduce bladder cancer risk, but other vegetables and fruits may not confer appreciable benefits against this cancer.
Mueller, et al. (“Terminal differentiation of human breast cancer through PPAR” Mol. Cell 1:465–470, 1998) suggests that the PPAR gamma transcriptional pathway can induce terminal differentiation of malignant breast epithelial cells.
Ramamoorthy, et al. (“AhR-mediated antiestrogenicity of diindolylmethane and analogs in vivo and in vitro,” Organohalogen Compounds, 37:321–324, 1998) suggests that DIM and substituted DIMs inhibit estrogen-induced uterine activities and breast cancer cell growth.
Safe (“2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related environmental antiestrogens: characterization and mechanism of action,” in Endocrine Disrupters, Naz (ed.), CRC Press, Boca Raton, Fla., pp. 187–221, 1999) suggests that selective Ah receptor modulators (SahRMs) are effective inhibitors of mammary tumor growth with clinical potential for treatment of breast cancer.
Suh, et al. (“A new ligand for the peroxisome proliferator-activated receptor-PPAR, GW7845, inhibits rat mammary carcinogenesis” Cancer Res. 59:5671–5673, 1999) suggests the use of a ligand for peroxisome proliferator-activated receptor-gamma to prevent experimental breast cancer.
Tontonoz, et al. (“Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor and the retinoid X receptor” Proc. Natl. Acad. Sci. USA 94:237–241, 1997) offers that PPAR gamma ligands such as thiazolidinediones and RXR-specific retinoids may be useful therapeutic agents for the treatment of liposarcoma.
Zhou, et al. (“Inhibition of murine bladder tumorigenesis by soy isoflavones via alterations in the cell cycle, apoptosis and angiogenesis” Cancer Res., 58:5231–5238, 1998) suggests that soy isoflavones can inhibit bladder tumor growth through a combination of direct effects on tumor cells and indirect effects on the tumor neovasculature.
Cancer is one of the leading causes of premature death in most developed countries. Since 1990, more than five million people have died from various forms of cancer. Presently, many cancer treatments are ineffective, or display significant negative side effects. Thus, there exists a need for the development of new and more effective treatments of cancer.